This invention relates a method of making a fluoroanthranilic acid. In particular, it relates to a method of making 4,5-difluoroanthranilic acid from 4,5-difluorophthalic anhydride in a single pot process without isolating any intermediate product.
The compound 4,5-difluoroanthranilic acid (DFAA) can be used as a pharmaceutical intermediate for making antibacterials. Previously, DFAA was made by treating 4,5-difluorophthalic anhydride (DFPAN) with ammonia to produce 4,5-difluorophthalamic acid (DFPA), which underwent a Hofmann rearrangement when treated with an aqueous solution of sodium hypochlorite in the presence of a base to lead ultimately, after acidification, to DFAA: ##STR2##
That reaction is described in U.S. Pat. No. 4,521,616.
Although that reaction works well on a laboratory scale, it presents several difficulties on scaling up. Specifically, the maximum amount of bleach (i.e., active NaOCl) that can be used in the reaction cannot exceed 15% because more concentrated bleach solutions are not stable. Therefore, relatively high dilution conditions are needed for the reaction to run successfully. In addition, because of the high dilutions that are needed, the cost of the aqueous disposal system is excessive.